FDA-Approved Compounds Show Promise in Treating Pseudomonas Aeruginosa Infections
Researchers have identified a combination of FDA-approved compounds that effectively inhibit the ExoU toxin produced by Pseudomonas aeruginosa, a bacterium responsible for severe infections such as microbial keratitis. The study screened 3,034 FDA-approved compounds and found zinc pyrithione, bismuth subcitrate, and polymyxin B to be effective in inhibiting ExoU without affecting human cells. These compounds work through distinct mechanisms, such as disrupting ExoU oligomerization and protein stability, impairing membrane association, and directly inhibiting catalysis. The combination of these compounds significantly reduced ExoU-mediated cytotoxicity in various models, including ex vivo porcine corneas and in vivo mouse keratitis models, without reducing bacterial load. This research supports the potential repurposing of these compounds as an antivirulence strategy for treating P. aeruginosa infections. 
